Mannose-binding lectin-2 genotypes and recurrent late pregnancy losses.
BACKGROUND
Low levels of mannose-binding lectin (MBL) predispose to various infectious and inflammatory disorders and have been reported to be associated with recurrent early miscarriages. Recurrent late pregnancy losses (RLPL) in the second trimester is a rare but devastating syndrome where maternal rather than fetal causes are likely to play a stronger role than in early recurrent miscarriage.


METHODS
We identified 75 patients with at least two late losses of pregnancies with apparently normal fetuses between gestational week 14 and 30 among patients with recurrent pregnancy losses referred to our clinic. Polymorphisms in the MBL2 gene associated with plasma MBL levels were investigated in all patients and in 104 women with two or more children and no miscarriages. The patients were divided into three groups: one with clinical signs of cervical insufficiency, one positive for the lupus anticoagulant (LAC) and an idiopathic group.


RESULTS
Among all patients with RLPL, 26.7% had MBL2 genotypes associated with MBL deficiency compared with 12.5% in controls [odds ratio (OR) 2.55; 95% confidence interval (CI) 1.17-5.52; P < 0.02]. Among patients with clinical signs of cervical insufficiency or the LAC, the frequency of genotypes associated with MBL deficiency was not significantly increased. However, among 38 patients with idiopathic RLPL, 36.8% carried low-producing MBL2 genotypes, which was significantly more than in controls (OR 4.08, 95% CI 1.70-9.83, P = 0.001).


CONCLUSIONS
MBL deficiency is strongly associated with idiopathic RLPL. This may point towards a role for excessive inflammatory disturbances as a cause of the syndrome.
Christiansen
Ole B
OB
Fertility Clinic 4071, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. obc@pregnancyloss.dk
Nielsen
Henriette S
HS
Lund
Marie
M
Steffensen
Rudi
R
Varming
Kim
K
D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood; D005260:Female; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third
D017152:Antibodies, Antiphospholipid; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin